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  • The EMBO Journal (2008) 27, 1537 - 1548
  • doi:10.1038/emboj.2008.92

Published online: 15 May 2008

Downregulation of AMP-activated protein kinase by Cidea-mediated ubiquitination and degradation in brown adipose tissue

Jingzong Qi1,a, Jingyi Gong1,a, Tongjin Zhao1,a, Jie Zhao1, Penny Lam2, Jing Ye1, John Zhong Li2, Jiawei Wu1, Hai-Meng Zhou1 and Peng Li1

  1. Protein Science Laboratory of Ministry of Education, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing, China
  2. Department of Biology, Hong Kong University of Science and Technology, Clearwater Bay, Kowloon, Hong Kong

Correspondence to:

Hai-Meng ZhouPeng Li, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China. Tel.: +86 10 62797121; Fax: +86 10 62797123; E-mail: li-peng@mail.tsinghua.edu.cn

aThese authors contributed equally to this work

Received 11 October 2007; Accepted 11 April 2008

We previously showed that Cidea-/- mice are resistant to diet-induced obesity through the upregulation of energy expenditure. The AMP-activated protein kinase (AMPK), consisting of catalytic alpha subunit and regulatory subunits beta and gamma, has a pivotal function in energy homoeostasis. We show here that AMPK protein levels and enzymatic activity were significantly increased in the brown adipose tissue of Cidea-/- mice. We also found that Cidea is colocalized with AMPK in the endoplasmic reticulum and forms a complex with AMPK in vivo through specific interaction with the beta subunit of AMPK, but not with the alpha or gamma subunit. When co-expressed with Cidea, the stability of AMPK-beta subunit was dramatically reduced due to increased ubiquitination-mediated degradation, which depends on a physical interaction between Cidea and AMPK. Furthermore, AMPK stability and enzymatic activity were increased in Cidea-/- adipocytes differentiated from mouse embryonic fibroblasts or preadipocytes. Our data strongly suggest that AMPK can be regulated by Cidea-mediated ubiquitin-dependent proteosome degradation, and provide a molecular explanation for the increased energy expenditure and lean phenotype in Cidea-null mice.

  • Keywords:

    • AMPK,
    • brown adipose tissue,
    • Cidea,
    • protein degradation,
    • ubiquitination